Biodegradable endoprostheses and methods for their fabrication

ABSTRACT

Biodegradable endoprostheses are formed from amorphous polymers having desirable biodegradation characteristics. The strength of such amorphous polymers is enhanced by annealing to increase crystallinity without substantially increasing the biodegradation time.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims the benefit of provisional application60/885,700 (Attorney Docket No. 022265-000500US), filed on Jan. 19,2007, the full disclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical devices and methodsfor their fabrication. In particular, the present invention relates tothe fabrication of biodegradable endoprostheses, such as stents, havingenhanced strength and controlled persistence after implantation.

Stents are generally tubular-shaped devices which function to hold openor reinforce a segment of a blood vessel or other body lumen, such as acoronary artery, carotid artery, saphenous vein graft, or femoralartery. They also are suitable to support and hold back a dissectedarterial lining that could occlude the body lumen, to stabilize plaque,or to support bioprosthetic valves. Stents can be formed from variousmaterials, particularly polymeric and/or metallic materials, and may benon-degradable, biodegradable, or be formed from both degradable andnon-degradable components. Stents are typically delivered to the targetarea within the body lumen using a catheter. With balloon-expandablestents, the stent is mounted to a balloon catheter, navigated to theappropriate area, and the stent is expanded by inflating the balloon. Aself-expanding stent is delivered to the target area and released,expanding to the required diameter to treat the disease. Stents may alsoelute various drugs and pharmacological agents.

Of particular interest to the present invention, biodegradable stentsand other endoprostheses are usually formed from polymers which degradeby hydrolysis and other reaction mechanisms in the vascular or otherluminal environment over time. Usually, it will be desirable to have theendoprosthesis completely degrade after it has served its neededsupporting function in the body lumen. Typically, complete degradationwill be desired in less than two years, often less than one year, andfrequently in a matter of months after implantation. Many biodegradableendoprostheses, however, are persistent for longer than needed, oftenremaining in place long after the supporting or drug delivery functionhas ended. The extended persistence of many biodegradable endoprosthesesoften results from a desire to enhance their strength. The polymerconstruction materials are often strengthened, such as by incorporatingmaterials having a higher crystallinity, so that they provide desiredsupport but take longer to degrade than would otherwise be desirable.

For these reasons, it would be desirable to provide improvedendoprostheses and methods for their fabrication, where theendoprostheses have a controlled strength and persistence. Inparticular, it would be desirable to be able to enhance the strength ofcertain biodegradable materials so that they have an improved strengthwhen incorporated into stents and other endoprostheses withoutsubstantially lengthening their degradation periods. Moreover, it wouldbe desirable to allow for control of the degradation period in thefabrication process so that an endoprosthesis can be made with differentdegradation periods while retaining an enhanced strength. At least someof these objectives will be met by the inventions described below.

2. Description of the Background Art

Heat annealing and other treatments of filaments and other componentsused in stents are described in U.S. Pat. No. 5,980,564, U.S. Pat. No.6,245,103, and U.S. Pat. No. 6,626,939. Heat treatment of polymericstent coatings is described in commonly owned, copending application no.PCT/US07/81996, which designates the United States.

BRIEF SUMMARY OF THE INVENTION

The present invention provides improved biodegradable endoprostheses andmethods for their fabrication. The endoprostheses are formed from anamorphous, biodegradable polymer. The use of amorphous polymers isdesirable since they provide relatively short periods of biodegradation,usually less than two years, often less than one year, frequently lessthan nine months, and sometimes shorter than six months, or evenshorter. The present invention relies on modifying the amorphouspolymers to introduce a desired degree of crystallinity. It has beenfound by inventors herein that introducing crystallinity into theamorphous polymer increases the strength of the polymer so that it issuitable for use as an endoprosthesis without substantially lengtheningthe period of biodegradation after implantation.

The crystallinity of a highly amorphous polymer as defined will be below10% prior to modification. After modification, the crystallinity willusually be increased by at least 20% of the original crystallinity ofthe amorphous material, preferably by at least 100% of the originalcrystallinity of the amorphous material and more preferably by at least1000% of the original crystallinity of the amorphous material. Presentlypreferred polymer materials will have a crystallinity in the range from10% to 20% after modification as described herein below. As used herein,“crystallinity” refers to a degree of structural order or perfectionwithin a polymer matrix.

Crystallinity can be measured by differential scanning calorimetry(Reading, M. et al, Measurement of crystallinity in polymers usingmodulated temperature differential scanning calorimetry, in MaterialCharacterization by Dynamic and Modulated Thermal Analytical Techniques,ASTM STP 1402, Riga, A. T. et al. Ed, (2001) pp. 17-31.

Methods according to the present invention for fabricating biodegradableprostheses comprise providing a tubular body having an initial diameter,where the tubular body is composed at least partially of a substantiallyamorphous, biodegradable polymer. The tubular body is heated to atemperature above its glass transition temperature and below its meltingpoint. The tubular body is then cooled to increase the crystallinity ofthe polymer. Either before or after this annealing process, the tubularbody may be patterned into a structure capable of radial contraction andexpansion in order to provide a stent or other endoprosthesis.

Usually, the tubular body will be fabricated as part of the method.Fabrication can be by a variety of conventional processes, such asextrusion, molding, dipping, and the like. A preferred formation processcomprises spraying a polymer dissolved in a solvent onto a cylindricalmandrel or other structure. Optionally, additives, such asstrength-enhancing materials, drugs, or the like, may be dissolved inthe solvent together with the polymer so that the materials areintegrally or monolithically formed with the endoprosthesis tube.Alternatively, the methods could rely on obtaining a pre-formed polymertube from a supplier or other outside source.

The polymeric tubular body is usually formed as a substantiallycontinuous cylinder free from holes or other discontinuities. Thetubular body typically has an outside diameter in the range from 2 mm to10 mm, a thickness in the range from 0.01 mm to 0.5 mm, and may be cutinto lengths suitable for individual endoprostheses, typically in therange from 5 mm to 40 mm.

The tubular bodies may be formed from any amorphous polymer havingdesired degradation characteristics where the polymer may be modified tohave the desired strength characteristics in accordance with the methodsof the present invention. Exemplary amorphous polymers includepoly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers;polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers,poly orthoesters and copolymers, poly anhydrides and copolymers,polyiminocarbonates and copolymers and the like. A particularlypreferred polymer comprises a copolymer of L-lactide and glycolide,preferably with a weight ratio of 85% L-lactide to 15% glycolide.

The heating segment of the annealing process will typically be carriedout for a period of from 1 minute to 3 hours, and the cooling will betypically to a temperature at or below ambient. Other suitabletemperatures and times, however, are described in the DetailedDescription of the Invention, below.

The tubular body will be patterned into a suitable endoprosthesisstructure, typically by laser cutting or other conventional processes.The patterning will usually be performed after the annealing process,but could be performed before the annealing process. As a furtheralternative, it may be desirable to anneal the tubular body both beforeand after the patterning, and in some instances additional annealingsteps may be performed so that the stent could be subjected to three,four, or even more annealing steps during the fabrication process.

The endoprosthesis pattern can be any suitable pattern of the typeemployed in conventional endoprostheses. A variety of exemplary patternsare set forth in commonly owned, co-pending application Ser. No.11/______ (Attorney Docket No. 022265-000510US), filed on the same dayas the present application, the full disclosure of which is incorporatedherein by reference.

In addition to the fabrication methods, the present invention alsoprovides biodegradable prostheses comprising a tubular body composed atleast partially of a substantially amorphous, biodegradable polymer. Thebiodegradable polymer will have been treated to produce spherulitecrystals in the amorphous polymer to increase crystallinity by at least20% of the original crytallinity. Other preferred aspects of theprosthesis have been described above with respect to the methods offabrication.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram illustrating the principal steps of themethods of the present invention.

FIGS. 2A and 2B illustrate an exemplary stent structure which may befabricated using the methods of the present invention.

FIG. 3 illustrates the stent of FIGS. 2A and 2B in a radially expandedconfiguration.

FIG. 4 illustrates a stent pattern utilized in an Example of the presentapplication.

DETAILED DESCRIPTION OF THE INVENTION

Amorphous biodegradable polymers (less than 10% crystallinity) degradefaster than crystalline polymers but are weaker than crystallinepolymers and hence are not typically suitable for vascular implants,such as stents, which need sufficient strength to provide support to theblood vessel. The present invention provides for the modification ofamorphous polymeric materials to make them suitable for use asbiodegradable stents and other endoprostheses. Amorphous materialssuitable for modification according to the present invention include butare not limited to poly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers;polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers,poly orthoesters and copolymers, poly anhydrides and copolymers,polyiminocarbonates and copolymers and the like. An exemplary stent ismade from amorphous material of a copolymer of 85/15Poly(L-Lactide-co-Glycolide) and processed to increase crystallinity byat least 20% of original crystallinity, preferably by at least 100% ,more preferably by at least 1000% of original crystallinity In oneembodiment, the biodegradable stent substantially degrades in less than2 years, preferable less than 1 year, more preferable less than 9months.

In accordance with the present invention, the amorphous biodegradablepolymeric material is processed to increase its crystallinity, Increasedcrystallinity may increase the strength, storage shelf life, andhydrolytic stability of the polymer stent material. The processinitiates and/or enhances crystallinity in the polymeric material bynucleating and/or growing small size spherulite crystals in thematerial. Since the amorphous regions of the modified polymer arepreferentially broken down by hydrolysis or enzymatic degradation inbiological environment, the modified amorphous biodegradable polymer hasincreased crystallinity and increased material strength post processing.The increase in crystallinity can be achieved by ‘Modifications’described in present invention which include at least one of heating,cooling, pressurizing, addition of additives, crosslinking and otherprocesses.

The polymer material can be made into a tube by spraying, extrusion,molding, dipping or other process from a selected amorphous copolymer.The amorphous polymer tubing is optionally vacuumed to at least −25 in.Hg., annealed, and quenched to increase crystallinity. In oneembodiment, the tube is vacuumed at or below 1 torr at ambienttemperature to remove water and solvent. It is then annealed by heatingto a temperature above the glass transitional temperature but belowmelting temperature of the polymer material. Preferably, the annealingtemperature is at least 10° C. higher than the glass transitionaltemperature (Tg), more preferably being at least 20° C. higher, andstill more preferably being at least 30° C. higher than the Tg. Theannealing temperature is usually at least 5° C. below the melting point(Tm), preferably being at least 20° C. lower, and more preferably beingat least 30° C. lower than the Tm of the polymer material. The annealingtime is between 1 minute to 10 days, preferably from 30 minutes to 3hours, and more preferably from 1.5 hours to 2.5 hours.

In one embodiment, the annealed tube is quenched by fast cooling fromthe annealing temperature to a temperature at or below ambienttemperature over a period from 1 second to 1 hour, preferably 1 minuteto 30 minutes, and more preferably 5 minutes to 15 minutes. In anotherembodiment the annealed tune is quenched by slow cooling from theannealing temperature to at or below ambient temperature within 1 hourto 24 hours, preferably 4 hours to 12 hours, and more preferably 6 hoursto 10 hours. In some instances the heat treated tube is cooled to atemperature below ambient temperature for a period from 1 minute to 96hours, more preferably 24 hours to 72 hours, to stabilize the crystalsand/or terminate crystallization. This annealing and quenching processinitiates and promotes nucleation of crystals in the polymer andincreases the mechanical strength of the material. The initial annealingtemperature and the cooling rate can be controlled to optimize the sizeof the crystals and strength of the material. In a further embodiment,the unannealed and/or annealed tube is exposed to ebeam or gammaradiation, with single or multiple doses of radiation ranging from 5 kGyto 100 kGy, more preferably from 10 kGy to 50 kGy.

The stent or other endoprosthesis is patterned from a tube of the stentmaterial in an “expanded” diameter and subsequently crimped to a smallerdiameter and fitted onto a balloon of a delivery catheter. The stent ispatterned, typically by laser cutting, with the tubing diameter about 1to 1.3 times, preferably 1.1 to 1.5 times, more preferably 1.15 to 1.25times, larger the intended deployed diameter. For example, a stent cutat a 3.5 mm×18 mm outer diameter is crimped on a 3.0 mm×18 mm stentdelivery catheter. In a further embodiment, the unannealed and/orannealed stent is exposed to ebeam or gamma radiation, with single ormultiple doses of radiation ranging from 5 kGy to 100 kGy, morepreferably from 10 kGy to 50 kGy.

The stent material may lose some crystallinity during stent cutting. Insuch cases, the stent annealed after cutting and/or a second time tore-crystallize the polymer to a higher crystallinity. Thus, the cutstent may be annealed a second time as generally described above.Annealing followed by cooling as described above can be repeated one ormore times to further increase crystallinity. In a further embodiment,the heat treated stent is cooled below ambient temperature to lock inthe crystals or terminate crystallization for 1 minute to 96 hours, morepreferably 24 hours to 72 hours.

The treated stent or other endoprosthesis can be crimped onto a deliveryballoon using mechanical crimpers comprising of wedges such as crimpersfrom Machine Solutions, Fortimedix, or others. The stent can also becrimped by placing the stent in a shrink tube and stretching the shrinktube slowly at a rate of 0.1 to 2 inches/minutes, more preferably 0.2 to0.5 inches/minutes until the stent is crimped to the desired crimpeddiameter. During crimping, the stent is heated to a temperature of 20°C. below the Tg to 10° C. above the Tg for 30 minutes, more preferablyto 10° C. below the Tg to Tg, and most preferably at the Tg of the stentmaterial. This process facilitates or enables the stent to maintain thefinal crimped diameter. After crimping, the ability for the stent toremain the crimped diameter can further be improved by fixing the stentin the crimped diameter while exposing it to a temperature of 20° C.below the Tg to 10° C. above the Tg for 30 minutes, more preferably to10° C. below the Tg to Tg, and most preferably at the Tg of the stentmaterial, for 1 minute to 24 hours, more preferably 15 minutes to 1hour. After holding at this crimping temperature, it is preferred to fixthe stent in the crimped diameter while at or below ambient temperaturesuntil further processing (i.e., sterilization). The stent can either becrimped while it is on the balloon of the stent delivery catheter orfirst crimped alone and then slipped onto the balloon of the catheter.In a further embodiment, the crimped stent is cooled below ambienttemperature to lock in the crystals or terminate crystallization for 1minute to 96 hours, more preferably 24 hours to 72 hours.

In a preferred embodiment, the final crimped stent on the catheter issterilized by 25 to 30 kGy dose of ebeam, typically with a single doseof 30 kGy or with multiple smaller doses (eg. 3×10 kGy). The stentsystem is usually kept below ambient temperature before, during and/orafter multiple smaller doses of sterilization. The stent that has beenpackaged and sterilized can also be exposed to heat treatment like thatdescribed above. In one embodiment, the biodegradable polymer stent isheated at about the Tg of the biodegradable stent material duringexpansion of the stent. The temperature during expansion can range from10° C. above Tg to 10° C. below Tg.

Upon deployment of such stent, the processes provide means to minimizestent recoil to less than 10% after expansion from the crimped state toan expanded state.

Additives can be added to the endoprosthesis to affect strength, recoil,or degradation rate, or combinations thereof. Additives can also affectprocessing of biodegradable stent material, radiopacity or surfaceroughness or others. Additives can be biodegradable ornon-biodegradable. The additives can be incorporated in to thebiodegradable stent or polymer material by blending, extrusion,injection molding, coating, surface treatment, chemical treatment,mechanical treatment, stamping, or others or combinations thereof. Theadditives can be chemically modified prior to incorporation in to thebiodegradable stent material.

In one embodiment, the percentage in weight of the additives can rangefrom 0.01% to 25%, preferably 0.1% to 10%, more preferably 1% to 5%.

In one embodiment, the additive includes at least nanoclay, nanotubes,nanoparticles, exfoliates, fibers, whiskers, platelets, nanopowders,fullerenes, nanosperes, zeolites, polymers or others or combinationthereof.

Examples of nanoclay includes Montmorillonite, Smectites, Talc, orplatelet-shaped particles, modified clay or others or combinationthereof. Clays can be intercalated or exfoliated. Example of claysinclude Cloisite NA, 93A, 30B, 25A, 15A, 10A or others or combinationthereof.

Examples of fibers include cellulose fibers such as Linen, cotton,rayon, acetate; proteins fibers such as wool or silk; plant fiber; glassfiber; carbon fiber; metallic fibers; ceramic fibers; absorbable fiberssuch as polyglycolic acid, polylactic acid, polyglyconate or others.

Examples of whiskers include hydroxyapetite whiskers, tricalciumphosphate whiskers or others.

In another embodiment, the additives includes at least modified starch,soybean, hyaluronic acid, hydroxyapatite, tricarbonate phosphate,anionic and cationic surfactants such as sodium docecyl sulphate,triethylene benzylammonium chloride, pro-degradant such as D2W (fromSymphony Plastic Technologies), photodegradative additives such as UV-H(from Willow Ridge Plastics), oxidative additives such as PDQ (fromWillow Ridge Plastics), TDPA, family of polylactic acid and its randomor block copolymers or others.

In another embodiment, the additives include electroactive orelectrolyte polymers, hydroscopic polymers, dessicants, or others.

In one embodiment, the additive is an oxidizer such an acids,perchlorates, nitrates, permanganates, salts or other or combinationthereof.

In one embodiment, the additive is a monomer of the biodegradablepolymeric stent material. For example glycolic acid is an additive topolyglycolic acid or its copolymer stent material.

In one embodiment, the additive can be water repellent monomers,oligomers or polymers such as bees wax, low MW polyethylene or others.

In another embodiment, the additive can be water attractant monomers,oligomers or polymers such as polyvinyl alcohol, polyethylene oxide,glycerol, caffeine, lidocaine or other.

In one embodiment, the additive can affect crystallinity of thebiodegradable polymeric stent material. Example of additive of nanoclayto PLLA affects its crystallinity.

In another embodiment, the biodegradable polymeric stent material canhave increased crystallinity by cross-linking such as exposure toradiation such as gamma or ebeam. The cumulative radiation dose canrange from 1 kGray to 1000 KGray, preferably 5 to 100 KGray, morepreferably 10 to 30 KGray.

In one embodiment, yield strength for the biodegradable polymeric stentmaterial is at least 50% of ultimate strength, preferably at least 75%of ultimate strength, more preferably at least 90% of ultimate strength,in water at 37° C.

In one embodiment, the elastic modulus for the biodegradable metallicstent material is at least 50 GPa, preferably at least 100 GPa, morepreferably at least 150 GPa.

In another embodiment, the elastic modulus for the biodegradablepolymeric stent material is at least 0.5 GPa, preferably at least 0.75GPa, more preferably at least 1 GPa, in water at 37° C.

In one embodiment, the yield strain for the biodegradable polymericstent material is at most 10%, preferably at most 5%, more preferably atmost 3%, in water at 37° C.

In one embodiment, the plastic strain for the biodegradable polymericstent material is at least 20%, preferably at least 30%, more preferablyat least 40%, in water at 37° C.

In one embodiment, the elastic recovery of the strained biodegradablepolymeric stent material is at most 15%, preferably at most 10%, morepreferably at most 5%, in water at 37° C.

In one embodiment, the biodegradable stent material degradessubstantially within 2 years, preferably within 1 year, more preferablywithin 9 months.

In one embodiment, the expanded biodegradable stent in physiologicalconditions at least after 1 month retains at least 25%, preferably atleast 40%, more preferably at least 70% of the strength or recoil

In one embodiment, the biodegradable polymeric stent materials degradesby at least bulk erosion, surface erosion, or combination thereof.

In one embodiment, the biodegradable polymeric stent material degradesby at least hydrolytic degradation, enzymatic degradation, oxidativedegradation, photo degradation, degradation under physiologicalenvironment or combination thereof.

The biodegradable polymeric stent material can have varying moleculararchitecture such as linear, branched, crosslinked, hyperbranched ordendritic.

The biodegradable polymeric stent material in this invention can rangefrom 10 KDa to 10,000 KDa in molecular weight, preferably from 100 KDato 1000 KDa, more preferably 300 KDa to 600 KDa.

In another embodiment, the biodegradable stent material has increasedcrystallinity by increasing orientation of polymer chains with in thebiodegradable stent material in radial and/or longitudinal direction bydrawing, pressurizing and/or heating the stent material. In anotherembodiment, the drawing, pressurizing and/or heating the stent materialoccurs simultaneously or sequentially.

In one embodiment, the biodegradable stent material is placed with atleast one surface against a non deformable surface and is pressurized toat least 200 psi, preferably to at least 300 psi, more preferably to atleast 500 psi. In another embodiment, the biodegradable stent materialis pressurized to at least 200 psi, preferably to at least 300 psi, morepreferably to at least 500 psi.

In one embodiment, the biodegradable stent material tube is placed within a larger diameter non deformable tube and is pressurized to at least200 psi, preferably to at least 300 psi, more preferably to at least 500psi. In another embodiment, the biodegradable stent material tube ispressurized to at least 200 psi, preferably to at least 300 psi, morepreferably to at least 500 psi.

In one embodiment, the biodegradable stent material has increasedcrystallinity by increasing the orientation of the polymer chains by atleast heating the biodegradable stent material above its glasstransition temperature (Tg) and below its melting temperature.

In one embodiment, the biodegradable stent material has increasedcrystallinity by heating the material to a temperature at least 10° C.higher than its Tg, preferably at least 20° C. higher, more preferablyat least 30° C. higher than the Tg of the biodegradable stent material.

In one embodiment, biodegradable stent material has increasedcrystallinity after drawing, heat and/or pressurizing and annealing atelevated temperature with or without vacuum. In one embodiment, theannealing temperature is below the temperature used for orientation ofthe polymer chains of the biodegradable stent material. In anotherembodiment, the annealing temperature is at most 20° C. below,preferably at most 15° C. below, more preferably at most 10° C. belowthe temperature for orientation of the polymer chains of thebiodegradable stent material.

In one embodiment, the biodegradable stent material after annealing isquenched below Tg of the biodegradable stent material, preferably atleast 25° C. below Tg, more preferably at least 50° C. below Tg of thebiodegradable stent material.

In one embodiment, the biodegradable polymeric stent material hasincreased crystallinity by using a combination of solvents, with onesolvent having solubility parameter with in 10% of the solubilityparameter of the polymer and the second solvent having solubilityparameter at least 10% different than the solubility parameter of thepolymer in the solvent.

In one embodiment the biodegradable polymer stent material has acrystallinity of greater than 10%, preferably greater than 25%, morepreferably greater than 50%.

The invention also provides means to improve consistency of strength,recoil or degradation rate of a biodegradable polymer stent material.

EXAMPLE

A tube is made by spraying an amorphous copolymerpoly(L-lactide-co-glycolide) with 85% lactide and 15% glycolide. Thepolymer and rapamycin analog can be dissolved in a solvent and can besprayed together to incorporate the rapamycin into the polymer stent. Amandrel is placed underneath an ultrasonic spray nozzle (MicromistSystem with Ultrasonic Atomizing Nozzle Sprayer, Sono-Tek, NY) which isrotating at 80 rpm and move longitudinally at a rate of 0.050inches/minutes. A solution of 11 to 1 ratio ofpoly(L-lactide-co-glycolide) and rapamycin analog on the mandrel. Theresulting tube has a thickness of 0.17 mm. The tube is heated at 45° C.for about 60 hours, annealed at 90° C. for 2 hours, and cooled toambient or room temperature with in 10 seconds. The annealed tube isthen cut with a UV laser to the design shown in FIG. 4 (shown in itscrimped state). The cut stent is annealed at 90° C. and slowly cooledfrom the annealing temperature to ambient temperature within eighthours. The stent delivery system is then packaged in a pouch andsterilized by gamma radiation.

The heat treated stent has higher radial strength than the non-treatedstent (Table 1).

TABLE 1 Comparison of Radial Strength of Treated and Non-treated Stent.No Heat Heat Type Treatment Treatment Radial Strength After LaserCutting Stent 7 Psi 14 Psi Radial Strength After Crimping Stent 6 Psi 9Psi Radial Strength After 30kGy Ebeam Sterilization 3 Psi 8 Psi RadialStrength when expanded at Tg n/a 12.5 Psi

Thus, as shown in FIG. 1, methods according to the present inventioninitially provide for a tubular body composed of an amorphous polymer,where the tubular body may be formed by extrusion, molding, dipping, orthe like, but is preferably formed by spraying onto a mandrel. Thetubular body is annealed to increased crystallinity and strength,usually by the heating and cooling processes described above. Thetubular body is then patterned to form a stent or other endoprosthesis,typically by laser cutting, usually after at least one annealingtreatment. Optionally, the tubular body may be treated both before andafter patterning, and may be treated by annealing more than once bothbefore and after the patterning.

Referring now to FIGS. 2A and 2B, a stent 10 suitable for modificationby the present invention has base pattern including a plurality ofadjacent serpentine rings 12 joined by axial links 14. As illustrated,the stent 10 includes six adjacent serpentine rings 12, where each ringincludes six serpentine segments comprising a pair of axial struts 16joined by a hinge-like crown 18 at one end. The number of rings andsegments may vary widely depending on the size of the desired size ofthe stent. According to the present invention, a supporting feature 20is disposed between adjacent axial struts 16 and connected so that itwill expand, usually elongate, circumferentially with the struts, asshown in FIG. 3. The supporting features 20 are in a generally closedU-shaped configuration prior to expansion, as shown in FIGS. 2A and 2B,and open into a shallow V-shape along with the opening of the axialstruts 16 about the crowns 18 during radial expansion of the serpentinerings 12, as shown in FIG. 3. Supporting features 20 enhance the hoopstrength of the stent after radial expansion, help resist recoil afterexpansion is completed, and provide additional area for supporting thevascular or other luminal wall and optionally for delivering drugs intothe luminal wall.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

1. A method for fabricating a biodegradable prosthesis, said methodcomprising: providing a tubular body having an initial diameter, whereinsaid tubular body is composed at least partially of a substantiallyamorphous biodegradable polymer; wherein the tubular body undergoesmodifications to increase the crystallinity of the polymer.
 2. A methodis claim 1 where in the tubular body undergoes patterning into astructure capable of radial contraction or expansion.
 3. A method as inclaim 1, where in the modification comprises heating the tubular body toa temperature above the glass transition temperature of the polymer andbelow the melting point of the polymer.
 4. A method as in claim 1, wherein the modification comprises at least one of heating, cooling,pressurizing, cross-linking and additions of additives.
 5. A method forfabricating a biodegradable prosthesis, said method comprising:providing a tubular body having an initial diameter, wherein saidtubular body is composed at least partially of a substantially amorphousbiodegradable polymer, while the diameter remains substantiallyunchanged; heating the tubular body to a temperature above a glasstransition temperature of the polymer and below the melting point of thepolymer; cooling the tubular body to increase the crystallinity of thepolymer; and patterning the tubular body into a structure capable ofradial contraction and expansion.
 6. A method as in claim 5, wherein thesubstantially amorphous polymer has a crystallinity below 10% by weightprior to heating and cooling.
 7. A method as in claim 6, wherein thepolymer has a increased crystallinity by at least 20% of originalcrystallinity after heating and cooling.
 8. A method as in claim 6,wherein the polymer has a increased crystallinity crystallinity by atleast 100% of original crystallinity after heating and cooling.
 9. Amethod as in claim 5, wherein providing the tubular body comprisesforming the tubular body by a process selected from the group consistingof extruding, molding, and dipping.
 10. A method as in claim 5, whereinproviding the tubular body comprises spraying the polymer dissolved in asolvent onto a cylindrical structure.
 11. A method as in claim 10,wherein an additive is dissolved in the solvent.
 12. A method as inclaim 5, wherein the tubular body has an outside diameter in the rangefrom 2 mm to 10 mm, a length in the range from 0.01 mm to 0.5 mm, and awall thickness in the range from 5 mm to 40 mm.
 13. A method as in claim5, wherein the polymer is selected from the group consisting ofpoly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers;polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers,poly orthoesters and copolymers, poly anhydrides and copolymers,polyiminocarbonates and copolymers.
 14. A method as in claim 5, whereinthe polymer comprises a copolymer of L-lactide and glycolide.
 15. Amethod as in claim 14, wherein the copolymer is 85% L-lactide and 15%glycolide by weight.
 16. A method as in claim 5, wherein the tubularbody is heated to a temperature at least 10° C. above the glasstransition temperature and at least 5° C. below the melting temperaturefor a period in the range from 1 minute to 3 hours.
 17. A method as inclaim 16, wherein the tubular body is cooled at or below ambienttemperature.
 18. A method as in claim 5, wherein the tubular body ispatterned after heating or cooling.
 19. A method as in claim 5, whereinthe tubular body is patterned before heating or cooling.
 20. A method asin claim 5, wherein patterning comprises laser cutting.
 21. A method asin claim 20, wherein the cut tubular structure comprises a plurality ofaxially linked serpentine rings.
 22. A method as in claim 5, wherein thetubular body is heated and cooled through at least one additional cycleafter patterning.
 23. A method as in claim 5, further comprisingincorporating a substance into the tubular body.
 24. A method as inclaim 23, wherein the substance comprises a drug selected to inhibitrestenosis of a blood vessel.
 25. A method as in claim 23, wherein thesubstance is an additive selected to enhance strength of the prosthesis.26. A method as in claim 25, wherein the additive is selected from thegroup consisting of nanoclay, nanotubes, nanoparticles, exfoliates,fibers, whiskers, platelets, nanopowders, fullerenes, nanosperes, andzeolites.
 27. A method as in claim 25, wherein the additive is selectedfrom the group consisting of montmorillonite, smectites, talc,platelet-shaped particles and modified clay.
 28. A method as in claim25, wherein the additive is a clay selected from the group consisting ofCloisite NA, 93A, 30B, 25A, 15A, and 10A.
 29. A method as in claim 25,wherein the additive is a fiber selected from the group consisting oflinen, cotton, rayon, acetate; wool, silk; plant fibers; glass fibers;carbon fibers; metallic fibers; ceramic fibers; and absorbable fibers.30. A method as in claim 25, wherein the additive is a whisker selectedfrom the group consisting of hydroxyapetite whiskers, tricalciumphosphate whiskers.
 31. A method as in claim 25, wherein the additive isselected from the group consisting of modified starch, soybean,hyaluronic acid, hydroxyapatite, and tricarbonate phosphate.
 32. Amethod as in claim 25, wherein the additive is an anionic or cationicsurfactant selected from the group consisting of sodium docecylsulphate, and triethylene benzylammonium chloride.
 33. A method as inclaim 25, wherein the additive is selected from the group consisting ofpro-degradants, photodegradative additives, and oxidative additives. 34.A method as in claim 25, wherein the additive is selected from the groupconsisting of electroactive polymers, electrolyte polymers, hydroscopicpolymers, and dessicants.
 35. A method as in claim 25, wherein theadditive is an oxidizer selected from the group consisting of acids,perchlorates, nitrates, permanganates, and salts thereof.
 36. A methodas in claim 25, wherein the additive is a water repellent polymerselected from the group consisting of bees wax and low MW polyethylene.37. A method as in claim 25, wherein the additive is a water attractantselected from the group consisting of polyvinyl alcohol, polyethyleneoxide, glycerol, caffeine, and lidocaine.
 38. A biodegradable prosthesiscomprising: a tubular body composed at least partially of asubstantially amorphous biodegradable polymer, wherein the biodegradablepolymer is substantially amorphous but has undergone modification toincrease crystallinity by at least 20% of original cyrstallinity.
 39. Abiodegradable prosthesis as in claim 38, having a crystallinity in therange from 10% to 40%.
 40. A biodegradable prosthesis as in claim 38,wherein the polymer is selected from the group consisting ofpoly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers;polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers,poly orthoesters and copolymers, poly anhydrides and copolymers,polyiminocarbonates and copolymers.
 41. A biodegradable prosthesis as inclaim 40, wherein the polymer comprises a copolymer of L-lactide andglycolide.
 42. A biodegradable prosthesis as in claim 41, wherein thecopolymer is 85% L-lactide and 15% glycolide by weight.
 43. Abiodegradable prosthesis as in claim 38, wherein the modificationcomprises at least one cycle of heating and cooling.
 44. A biodegradableprosthesis as in claim 42, wherein the modification comprises at leastthe cycles of heating and cooling.